The KRAS-variant is associated with risk of developing double primary breast and ovarian cancer.
The KRAS-variant is associated with risk of developing double primary breast and ovarian cancer.
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DOI：
10.1371/journal.pone.0037891
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Shulman LP
中科院分区：
文献类型：
--
作者：
Pilarski R;Patel DA;Weitzel J;McVeigh T;Dorairaj JJ;Heneghan HM;Miller N;Weidhaas JB;Kerin MJ;McKenna M;Wu X;Hildebrandt M;Zelterman D;Sand S;Shulman LP
一种生殖系microRNA结合位点破坏变体，KRAS变体（rs61764370），与发展几种癌症的风险增加有关。由于该变异与遗传性乳腺癌和卵巢癌家族（HBOC）患者的卵巢癌风险以及绝经前三阴性乳腺癌风险密切相关，因此我们评估了KRAS变异与乳腺癌和卵巢癌个人病史（称为双原发患者）的相关性。对来自双原发患者的生殖系DNA进行KRAS变体检测（n = 232）。 获得病理诊断的确认、诊断年龄、卵巢癌诊断和样本采集之间的间隔、其他癌症诊断和家族史（如可用）。所有患者均接受有害BRCA突变检测。KRAS变异体在无信息（BRCA阴性）的双原发患者中显著富集，在卵巢癌诊断后两年内累积的患者中发现了39%。此外，在绝经后诊断为卵巢癌的无信息双原发患者中发现了35%的KRAS变异体，并且与具有阳性家族史的无信息双原发患者显著相关。KRAS变异体在发展超过两种原发性癌症的无信息患者中也显著富集，在48%的患有两种乳腺原发性癌症加卵巢癌或三种原发性癌症的女性中发现。这些发现进一步验证了KRAS变异在乳腺癌和卵巢癌风险中的重要性，并支持该变异作为先前被认为无信息的HBOC家族的遗传标记的关联。
A germline microRNA binding site-disrupting variant, the KRAS-variant (rs61764370), is associated with an increased risk of developing several cancers. Because this variant is most strongly associated with ovarian cancer risk in patients from hereditary breast and ovarian families (HBOC), and with the risk of premenopausal triple negative breast cancer, we evaluated the association of the KRAS-variant with women with personal histories of both breast and ovarian cancer, referred to as double primary patients. Germline DNA from double primary patients was tested for the KRAS-variant (n = 232). Confirmation of pathologic diagnoses, age of diagnoses, interval between ovarian cancer diagnosis and sample collection, additional cancer diagnoses, and family history were obtained when available. All patients were tested for deleterious BRCA mutations. The KRAS-variant was significantly enriched in uninformative (BRCA negative) double primary patients, being found in 39% of patients accrued within two years of their ovarian cancer diagnosis. Furthermore, the KRAS-variant was found in 35% of uninformative double primary patients diagnosed with ovarian cancer post-menopausally, and was significantly associated with uninformative double primary patients with a positive family history. The KRAS-variant was also significantly enriched in uninformative patients who developed more then two primary cancers, being found in 48% of women with two breast primaries plus ovarian cancer or with triple primary cancers. These findings further validate the importance of the KRAS-variant in breast and ovarian cancer risk, and support the association of this variant as a genetic marker for HBOC families previously considered uninformative.
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影响因子：
120.7
作者：
Walsh, T;Casadei, S;King, MC
通讯作者：
King, MC
影响因子：
11.2
作者：
Palma, Maurizia Dalla;Domchek, Susan M.;Nathanson, Katherine L.
通讯作者：
Nathanson, Katherine L.
影响因子：
4
作者：
Evans, D. Gareth;Ahmed, Munaza;Wallace, Andrew
通讯作者：
Wallace, Andrew
影响因子：
11.2
作者：
Chin LJ;Ratner E;Leng S;Zhai R;Nallur S;Babar I;Muller RU;Straka E;Su L;Burki EA;Crowell RE;Patel R;Kulkarni T;Homer R;Zelterman D;Kidd KK;Zhu Y;Christiani DC;Belinsky SA;Slack FJ;Weidhaas JB
通讯作者：
Weidhaas JB
影响因子：
8.8
作者：
Metcalfe, K. A.;Finch, A.;Narod, S. A.
通讯作者：
Narod, S. A.